Cultured mouse fibroblasts which are transformed by RNA viruses, a DNA virus or a chemical agent, all secrete a 35,000 Mr-glycoprotein (major excreted protein, MEP) in large amounts. Nontransformed murine fibroblasts secrete this protein in much lower amounts. These fibroblasts and cultured primary mouse epidermal cells, the target for tumor promoters in vivo, can be stimulated to release MEP by treatment with tumor promoters. We have purified this protein and prepared antisera against it. The protein, of unknown biologic function, undergoes extensive modification prior to secretion. We are studying this system as a model of regulation of protein synthesis, processing and secretion as it is affected by transformation and agents which mimic the transformed state, such as tumor promoters.